The effect of dietary protein on nitrogen and sulfur metabolism in portacaval-shunted rats

The effect of varying the amount of protein in the diet on postoperative recovery, plasma ammonia, urinary orotic acid and metabolism of sulfur-containing amino acids was examined in rats with portacaval shunts (PCS). Food intake and weight gain were lower in both PCS and control rats fed a low (6%) casein diet unsupplemented with methionine compared with rats fed an adequate (18%) casein diet. PCS rats fed 60% casein ate slightly less and took longer to recover their preoperative body weight compared to 60% controls. Shunted rats were consistently hyperammonemic and orotic aciduric compared to controls. Increasing protein in the diet elevated plasma ammonia and urinary orotic acid in all rats to levels above those of the rats fed 18% casein, but the effect was greater in rats with PCS. After i.p. injection of L-[35S]methionine or L-[35S]cysteine, urinary 35S and [35S]sulfate excretion increased and [35S]taurine and total taurine excretion decreased in all rats fed 60% casein. These changes are consistent with our observation that hepatic activities of cysteine dioxygenase and cysteine sulfinate:alpha-ketoglutarate aminotransferase increased and that of cysteine sulfinate decarboxylase decreased in rats fed the high protein diet. The effect of dietary treatment on both urinary taurine excretion and decarboxylase activity was greater in PCS rats than in controls. Although PCS rats fed a high protein diet may have a decreased taurine-synthesizing capability compared to controls, their ability to oxidize a methionine or cysteine load to sulfate is not compromised by feeding either an 18 or 60% casein diet.     

Hepatic cysteine sulfinic acid decarboxylase activity in rats fed various levels of dietary casein

A series of experiments was conducted to examine the effects of dietary protein intake on hepatic cysteine sulfinic acid decarboxylase (EC 4.1.1.29) activity and urinary taurine excretion. When rats were fed diets containing 18, 30, 45 or 60% casein for 1 wk, hepatic cysteine sulfinic acid decarboxylase activity (CSAD) decreased in a progressive and significant manner. Enzyme activity in rats fed a 60% casein diet was 25% of the activity measured in rats fed 18% casein. The time course of the change in CSAD activity was examined in rats fed a 60% casein diet. Within 24 h of switching rats from a moderate (18% casein) to high (60% casein) protein diet, enzyme activity decreased by 50% and continued to decline in rats fed the high protein diet for 7 d. The observed decrease in enzyme activity was reversed when rats were refed the 18% casein diet. The half-life of CSAD was calculated to be 2 and 7 d during the diet switch from 18 to 60% casein and from 60 to 18% casein, respectively. The change in enzyme activity was evident after a single high protein meal. In contrast to CSAD activity, urinary taurine excretion increased 140-fold within 2 d of switching rats from an 18 to 60% casein diet. Upon refeeding of the 18% casein diet taurine excretion rapidly decreased. These findings indicate that CSAD responds in a rapid and reversible manner to dietary protein.     

Interaction of dietary protein differing in sulfur amino acid content and pectin on bile acid conjugation in immature and mature rats

Rapidly growing immature (4-wk-old) and slowly growing mature (15-wk-old) rats were fed fiber-free or 10 g/100 g pectin diets containing various proteins differing in the sulfur amino acid content for 30-32 d. Soybean protein, casein, whole egg protein and egg albumen were used at the nitrogen level of 2.7 g/100 g diet. These experimental diets contained 0.354, 0.540, 0.945 and 1.22 g sulfur amino acids/100 g, respectively. In the rats fed fiber-free diets, a substantial quantity of glycine-conjugated bile acids was detected in the bile of immature rats fed soybean protein and casein (73 and 25% of total bile acids, respectively), but not in the other groups (less than 13%). Dietary pectin increased bile acid excretion both in immature (48-77%) and mature (34-114%) rats irrespective of the protein source, except in immature rats fed egg albumen and mature rats fed whole egg protein. Because a pectin-dependent increase in bile acid excretion was essentially attributed to the increase in glycine-conjugates, this dietary fiber significantly increased the ratio of glycine-conjugates to taurine-conjugates (2.4- to 6.5-fold). This increase was accompanied by a 40-50% decrease in the concentration of liver taurine, except in immature rats fed soybean protein and egg albumen. However, there was no consistent relationship between the extent of taurine conjugation and the activity of liver cysteine dioxygenase, one of the rate-limiting enzymes in taurine synthesis.     

Effect of the quality of dietary amino acids composition on the urea synthesis in rats

We have shown that urinary urea excretion increased in rats given a lower quality protein. The purpose of present study was to determine whether the composition of dietary amino acids affects urea synthesis. Experiments were done on three groups of rats given diets containing a 10% gluten amino acid mix diet or 10% casein amino acid mix diet or 10% whole egg protein amino acids mix diet for 10 d. The urinary excretion of urea, the liver concentration of N-acetylglutamate, and the liver concentration of free serine, glutamic acids and alanine were greater in the group given the amino acid mix diet of lower quality. The fractional and absolute rates of protein synthesis in tissues declined with a decrease in quality of dietary amino acids. The hepatic concentration of ornithine and the activities of hepatic urea-cycle enzymes were not related to the urea excretion. These results suggest that the increased concentrations of amino acids and N-acetylglutamate seen in the liver of rats given the amino acid mix diets of lower quality are likely among the factors stimulating urea synthesis. The protein synthesis in tissues is at least partly related to hepatic concentrations of amino acids. The composition of dietary amino acids is likely to be one of the factors regulating urea synthesis when the quality of dietary protein is manipulated.     

Effect of supplementing low protein diets with the limiting amino acids on the excretion of N1-methylnicotinamide and its pyridones in rats

We have hypothesized that the ratio of the excreted by-products of niacin metabolism, N1-methyl-2-pyridone-5-carboxamide (2-pyr) + N1-methyl-4-pyridone-3-carboxamide (4-pyr)/N1-methylnicotinamide (MNA), might be useful as an index to assess the adequacy of amino acid intake in rats. The experiment reported herein was performed to test this hypothesis. When a 10, 20 or 40% casein diet supplemented with 0.1, 0.2 or 0.4% L-methionine, respectively, was fed to rats, the urinary excretion of MNA decreased, and that of 4-pyr increased, as the level of dietary casein and methionine increased. Therefore, the ratio of (2-pyr + 4-pyr)/MNA increased with increasing dietary casein and methionine levels. When the limiting amino acids of casein or soy protein isolate were added to a low casein or low soy protein isolate diet, the urinary ratio of (2-pyr + 4-pyr)/MNA also increased. These results indicate that the increased urinary ratio of (2-pyr + 4-pyr)/MNA can serve as a biological marker for adequate amino acid intake.     

Taurine and serine supplementation modulates the metabolic response to tumor necrosis factor alpha in rats fed a low protein diet.

Plasma taurine and serine decrease following trauma and in severe inflammatory disease. These changes may signify an increase in requirements for sulfur amino acids. We previously demonstrated that cysteine supplementation can restore the impaired ability of rats fed an 8% casein diet to increase hepatic zinc, glutathione (GSH) and protein concentrations in response to tumor necrosis factor alpha (TNF alpha). Here we examined whether serine or taurine produces a similar effect, because serine provides the carbon skeleton of cysteine and taurine is its major metabolite. After 7 d of receiving either a 20% casein diet supplemented with cysteine or an 8% casein diet supplemented with alanine, serine or taurine, rats received an intraperitoneal injection of human TNF alpha. Tumor necrosis factor caused no change in hepatic GSH but resulted in a lower GSH concentration in lung in rats fed the alanine-supplemented diet. Neither taurine nor serine increased liver GSH relative to that in rats fed alanine, but the depression in lung due to TNF injection was lessened. The absolute increase in ceruloplasmin in response to TNF was enhanced in rats fed the alanine-supplemented diet relative to those fed the 20% casein diet. Serine normalized this response. This observation--the effects of taurine and serine on lung GSH and a significant negative correlation between ceruloplasmin and liver and lung GSH concentration in rats fed TNF--suggests that supplemental serine and taurine may improve antioxidant defenses when dietary supplies of cysteine are low but do not influence cysteine availability for a normal response to TNF.     

Activity of L-cysteinesulfinate carboxy-lyase and persulfurase in livers of rats fed different levels of sulfate and cysteine.

Activity of L-cysteinesulfinate carboxy-lyase (CSC) and persulfurase was measured in livers of rats fed 15% casein diets supplemented with (1) 0.53% cysteine, (2) 0.40% cysteine, (3) 0.40% cysteine + 0.10% sulfate, (4) 0.42% sulfate, or (5) 0.42% sulfate + 0.40% cysteine. The diets were fed to adult rats for 1 week and to weanling rats for periods of 1 and 4 weeks. At the end of each feeding period, the highest CSC activity was detected in livers from animals fed diet 4, but no differences in CSC activity were detected among livers from the other four groups. Persulfurase activity did not differ significantly among those weanling or adult rats fed the diets for 1 week but was lower among those fed diet 4 than diet 5 for 4 weeks. The acitivity patterns did not parallel those of taurine excretion or conjugation observed previously among rats fed the same diets, and may indicate that factors other than taurine synthesis and ingestion control those processes.     

Effect of dietary tryptophan levels on the urinary excretion of nicotinamide and its metabolites in rats fed a niacin-free diet or a constant total protein level

We previously found that the sum total urinary excretion of nicotinamide and its metabolites in growing rats did not increase as the level of dietary casein increased. So, we investigated how the urinary excretion of nicotinamide and its metabolites changed when rats were fed nicotinic acid-free diets containing 10, 20 or 40% casein, or when they were fed diets containing nicotinic acid and the same level of protein but different levels of tryptophan. The latter diets were 10% casein-30% gelatin, 20% casein-20% gelatin or 40% casein. With the nicotinic acid-free diets, the sum total urinary excretion of nicotinamide and its metabolites was almost the same in the groups fed the 20 and 40% casein diets; however, it was significantly lower in the group fed the 10% casein diet. With diets containing the same level of protein, the sum total urinary excretion of these compounds in the groups fed the 10% casein-30% gelatin, 20% casein-20% gelatin and 40% casein diets were about 5, 7 and 11 mumol/d, respectively, values that were significantly different from each other. Therefore, it was found that only when the total protein intake was constant did the sum total urinary excretion of nicotinamide and its metabolites increase with increasing intake of tryptophan.     

Dietary taurine alters ascorbic acid metabolism in rats fed diets containing polychlorinated biphenyls

The effect of dietary taurine on ascorbic acid metabolism and hepatic drug-metabolizing enzymes was investigated in rats fed diets containing polychlorinated biphenyls (PCB) to determine whether taurine has an adaptive and protective function in xenobiotic-treated animals. Young male Wistar rats (60 g) were fed diets containing 0 or 0.2 g/kg diet PCB with or without 30 g/kg diet of taurine for 14 d. The rats fed the PCB-containing diets had greater liver weight, higher ascorbic acid concentrations in the liver and spleen and greater hepatic cytochrome P-450 contents than control rats that were not treated with PCB (P < 0.01). In PCB-fed rats, urinary ascorbic acid excretion was enhanced, and serum cholesterol concentration (especially HDL-cholesterol) was significantly elevated compared with those in control rats. Dietary taurine significantly potentiated the increases in the urinary excretion of ascorbic acid and the rise in the levels of cytochrome P-450 which were caused by PCB treatment. On the other hand, the supplementation of taurine to control diet did not alter these variables. Taurine may enhance the hepatic drug-metabolizing systems, leading to the stimulation of the ascorbic acid metabolism in rats fed diets containing PCB.     

A soy protein diet alters hepatic lipid metabolism gene expression and reduces serum lipids and renal fibrogenic cytokines in rats with chronic nephrotic syndrome

Nephrotic syndrome (NS) is characterized by the presence of proteinuria and hyperlipidemia. However, ingestion of soy protein has a hypolipidemic effect. The present study was designed to determine whether the ingestion of a 20% soy protein diet regulates the expression of hepatic sterol regulatory element binding protein (SREBP)-1, fatty acid synthase (FAS), malic enzyme, beta-hydroxy-beta-methylglutaryl-CoA (HMG-CoA) reductase (r) and synthase (s), and LDL receptor (r), and to assess whether soy protein improves lipid and renal abnormalities in rats with chronic NS. Male Wistar rats were injected with vehicle or with puromycin aminonucleoside to induce NS and were fed either 20% casein or soy protein diets for 64 d. NS rats fed 20% soy protein had improved creatinine clearance and reduced proteinuria, hypercholesterolemia, hypertriglyceridemia, as well as VLDL-triglycerides and LDL cholesterol compared with NS rats fed the 20% casein diet. In addition, the soy protein diet decreased the incidence of glomerular sclerosis, and proinflammatory cytokines in kidney. Ingestion of the soy protein diet by control rats reduced the gene expression of SREBP-1, malic enzyme, FAS and increased HMG-CoAr, HMG-CoAs and LDLr. However, NS rats fed either casein or soy protein diets had low insulin concentrations with reductions in SREBP-1, FAS and malic enzyme expression compared with control rats fed the casein diet. NS rats fed the soy diet also had lower HMG-CoAr and LDLr mRNA levels than NS rats fed casein. In conclusion, the beneficial effects of soy protein on lipid metabolism are modulated in part by SREBP-1. However, in NS rats, the benefit may be through a direct effect of this protein on kidney rather than mediated by changes in expression of hepatic lipid metabolism genes.     

Enzymes and metabolites of cysteine metabolism in nonhepatic tissues of rats show little response to changes in dietary protein or sulfur amino acid levels

In liver, cysteine dioxygenase (CDO), cysteinesulfinate decarboxylase (CSD), and gamma-glutamylcysteine synthetase (GCS) play important regulatory roles in the metabolism of cysteine to sulfate, taurine and glutathione. Because glutathione is released by the liver and degraded by peripheral tissues that express gamma-glutamyl transpeptidase, some peripheral tissues may be exposed to relatively high concentrations of cysteine. Rats were fed diets that contained low, moderate or high concentrations of protein or supplemental cysteine or methionine for 2 wk, and CDO, CSD and GCS activities, concentrations and mRNA levels and the concentrations of cysteine, taurine and glutathione were measured in liver, kidney, lung and brain. All three enzymes in liver responded to the differences in dietary protein or sulfur amino acid levels, but only CSD in kidney and none of the three enzymes in lung and brain responded. Renal CSD activity was twice as much in rats fed the low protein diet as in rats fed the other diets. Changes in renal CSD activity were correlated with changes in CSD concentration. Some significant differences in cysteine concentration in kidney and lung and glutathione and taurine concentrations in kidney were observed, with higher concentrations in rats fed higher levels of protein or sulfur amino acids. In liver, the changes in cysteine level were consistent with cysteine-mediated regulation of hepatic CDO activity, and changes in taurine level were consistent with predicted changes in cysteine catabolism due to the changes in cysteine concentration and CDO activity. Changes in renal and lung cysteine, taurine or glutathione concentrations were not associated with a similar pattern of change in CDO, CSD or GCS activity. Overall, the results confirm the importance of the liver in the maintenance of cysteine homeostasis.     

Soy protein ameliorates metabolic abnormalities in liver and adipose tissue of rats fed a high fat diet

Chronic consumption of high-fat or -carbohydrate diets is associated with the development of obesity; however, it is not well established whether dietary protein plays a role in the development of abnormalities of lipid metabolism that occur during obesity. To determine the effect of different types of protein during diet-induced obesity on hepatic and adipocyte lipid metabolism, rats were fed casein (CAS) or soy (SOY) protein diets with 5% fat or high-fat diets with 25% fat (HF-CAS and HF-SOY) for 180 d. Rats fed soy diets had lower hepatic sterol regulatory element binding protein-1 (SREBP-1) expression and higher SREBP-2 expression than those fed casein diets, leading to less hepatic lipid deposition. On the other hand, long-term HF-SOY consumption prevented hyperleptinemia in comparison with rats fed HF-CAS. Rats fed soy protein diet showed higher adipocyte perilipin mRNA expression and smaller adipocyte area than those fed casein diets, which was associated with a lower body fat content. Furthermore, the lipid droplet area in brown adipose tissue was significantly lower in rats fed soy diets than in those fed casein diets and it was associated with higher uncoupling protein-1 (UCP-1) expression. As a result, rats fed the soy diets gained less weight than those fed the casein diets, in part due to an increase in the thermogenic capacity mediated by UCP-1. These results suggest that the type of protein consumed and the presence of fat in the diet modulate lipid metabolism in adipose tissue and liver.     

Oligo-L-methionine and resistant protein promote cecal butyrate production in rats fed resistant starch and fructooligosaccharide.

We examined the role of resistant protein and peptides in promoting cecal butyrate production in rats fed rapidly fermentable carbohydrates. Rats were fed diets containing raw potato starch (RPS, 200 g/kg diet) or fructooligosaccharide (FOS, 60 g/kg diet) with casein, soy or rice protein (250 g/kg diet) for 13 d. In rats fed RPS with casein, the major cecal organic acid was acetate (441 micromol), but lactate and succinate were also found in considerable amounts (324 micromol). Succinate was the major cecal organic acid (235 micromol) in rats fed FOS with casein. When rice protein was fed with RPS, the contribution of lactate was significantly lower and that of propionate tended to be higher (P < 0.1) than in rats fed casein. In rats fed rice protein with FOS, cecal butyrate and acetate were greater and cecal succinate was lower than in rats fed casein with FOS (P < 0.05). Despite the similar amounts of undigested protein in rice and soy proteins, soy protein did not similarly affect cecal butyrate in rats fed FOS or RPS. In another experiment, rats were fed diets containing high amylose cornstarch (HAS, 200 g/kg diet) with casein, casein + oligo-L-methionine (OM, 3 g/kg diet), soy protein, soy protein + OM (3 g/kg diet) or rice protein (250 g/kg diet) for 10 d. OM (digestibility, 31%) was substituted for the same amount of casein. Rats fed rice protein had greater cecal butyrate than rats fed casein (P < 0.05). OM supplementation to casein or soy protein increased cecal butyrate compared with rats fed casein or soy protein alone (P < 0.05). These data support our hypothesis that resistant protein and peptides promote cecal butyrate production and suggest that the differing potency of rice and soy proteins in promoting cecal butyrate production might be explained in part by the different amino acid composition of resistant protein.     

Altering dietary protein type and quantity reduces urinary albumin excretion without affecting plasma glucose concentrations in BKS.cg-m +Lepr db/+Lepr db (db/db) mice

Protein restriction is used conventionally in the prevention and treatment of diabetic nephropathy. Recently, the use of soy protein instead of animal protein has been postulated as a new preventive and treatment option. The aim of this study was to determine the qualitative and quantitative effects of dietary protein on biomarkers of diabetic nephropathy in a Type 2 diabetes mellitus mouse model (BKS.cg-m +Lepr(db)/+Lepr(db) mice). Diabetic (+Lepr(db)/+Lepr(db)) and control (m+/m+) mice (n = 24/group) consumed one of four different diets ad libitum [20% casein, 20% soy protein, 12% casein or 12% soy protein (energy-based percentages)] from 35 +/- 4 d of age until termination (184-217 d of age). Blood and urine were collected throughout the study to measure biomarkers of diabetes and diabetic nephropathy. Kidney tissue was collected at the end of the study for weight. In diabetic mice, a 20% casein diet increased urinary albumin excretion to macroalbuminuric levels, whereas a 20% soy protein diet led to no major changes in urinary albumin excretion. Low protein diets (12%), independently of protein type, decreased urinary albumin excretion to low microalbuminuric levels. There were no significant differences in plasma glucose concentrations. These findings show lower urinary albumin excretion when a soy protein diet or a low casein diet is fed, suggesting a delay in the progression of diabetic nephropathy.     

Relationship between amino acid composition of diet and plasma cholesterol level in growing rats fed a high cholesterol diet

The effects of dietary sulfur-containing amino acids and glycine on plasma cholesterol level were studied in rats fed amino acid mixture diets containing cholesterol. The relationship between the amino acid composition of dietary proteins and plasma cholesterol levels was also investigated in rats fed diets containing various kinds of protein such as casein, egg albumin, pork protein, fish protein, corn gluten, wheat gluten and soy protein. Feeding the amino acid mixture corresponding to casein led to an approximately two-fold level of plasma total cholesterol as compared with feeding the amino acid mixture corresponding to wheat gluten. It was possible to reduce the plasma cholesterol of rats fed the amino acid mixture of the casein type by increasing the proportion of cystine in the total sulfur amino acids. Inversely, the deprivation of cystine resulted in an enhancement of the plasma cholesterol of rats fed the gluten type amino acid mixture. Glycine had a tendency to resist increases in the plasma cholesterol level. A significant negative correlation was noted between plasma cholesterol levels and the content of cystine in intact dietary proteins. The results suggest that the differential effect of dietary proteins on plasma cholesterol level is mainly associated with sulfur-containing amino acids included in the protein, regardless of whether it is of animal or plant origin.     

The quality and quantity of dietary protein affect brain protein synthesis in rats.

The influence of the amino acid supply in diets with different quality and quantity of protein on the rate of protein synthesis in the brain was investigated. Amino acid concentrations in serum and brain altered in accordance with the amino acid levels of the diets, with the exception of some amino acids such as aspartic acid, glutamic acid, glycine and threonine. When rats were fed various levels of dietary casein (0, 5 and 20%), the aggregation of ribosomes increased and the fractional rate of protein synthesis tended to increase with the increase in dietary protein. When rats were fed a 20% casein diet, greater aggregation of brain ribosomes and protein synthesis rate were observed compared with those in rats fed 20% wheat gluten or gelatin diets. The RNA activity was related to the degree of the aggregation of brain ribosomes and the fractional rate of protein synthesis.     

Cysteine is the metabolic signal responsible for dietary regulation of hepatic cysteine dioxygenase and glutamate cysteine ligase in intact rats

Cysteine, rather than a precursor or metabolite of cysteine, appears to mediate the upregulation of cysteine dioxygenase (CDO) and the downregulation of glutamate cysteine ligase (GCL) in cultured primary rat hepatocytes. However, similar experiments in intact rats have not been performed to confirm in vivo that changes in hepatic cysteine levels are associated with the regulation of CDO or GCL activity. Therefore, rats were fed a low protein basal diet (100 g casein/kg diet) with or without supplemental sulfur amino acids (8 g cystine, 9 g homocystine or 10 g methionine/kg diet) and with or without propargylglycine (PPG, 1 mmol/kg), an irreversible inhibitor of cystathionine gamma-lyase. Rats were fed the assigned diet for 2 full days and up until the mid-point of the dark cycle on d 3, at which time they were killed for collection of liver. Rats fed the PPG-containing diets had hepatic cystathionine gamma-lyase activities that were approximately 16% of the uninhibited level. PPG treatment reduced CDO activity by 50 and 54%, increased GCL activity by 41 and 61% and lowered total cysteine concentration by 33 and 64% in liver of the homocystine and methionine-supplemented groups, respectively, but not in the cystine-supplemented groups or unsupplemented groups. Glutathione levels were not affected by PPG treatment in any groups. These experiments are consistent with a role for cysteine, rather than a precursor or metabolite of cysteine, in the metabolic signaling responsible for diet-induced regulation of CDO and GCL.     

Consumption of soy protein isolate modulates the phosphorylation status of hepatic ATPase/ATP synthase beta protein and increases ATPase activity in rats

ATPase/ATP synthase plays important roles in the regulation of carbohydrate, protein, and lipid metabolism through modulating energy homeostasis. The purpose of this study was to examine the effects of feeding soy proteins and isoflavones (ISF) on the enzymatic activity and protein modification of hepatic mitochondrial ATPase/ATP synthase. In Expt. 1, Sprague-Dawley rats aged 50 d were fed diets containing either 20% casein or 20% alcohol-washed soy protein isolate (SPI) with or without supplemental ISF (770.7 micromol/kg diet) for 70 d. In Expt. 2, weanling Sprague-Dawley rats were fed diets containing 20% casein with or without added ISF (154.1 micromol/kg diet) or 20% SPI for 90 d. Hepatic mitochondrial ATPase activity was significantly higher in the rats fed SPI than in those fed casein. Addition of ISF to SPI eliminated the action of SPI. ATPase/ATP synthase beta protein contents in the liver were unchanged; however, its patterns measured by 2-dimensional Western blot were different among dietary groups. The rats fed SPI or SPI plus ISF had 3 more major protein spots with the same molecular weights (80 kDa and 55 kDa) as those presented in the rats fed casein but with different isoelectric points. Pretreatment of hepatic mitochondrial proteins from the rats fed casein with alkaline phosphatase produced the same ATPase/ATP synthase beta patterns as observed in the SPI-fed rats and significantly elevated the ATPase activity. These results suggest that consumption of soy proteins increases hepatic ATPase activity, which might be a consequence of increased dephosphorylation or decreased phosphorylation of the mitochondrial ATPase/ATP synthase beta protein.     

Histidine-imbalanced diets stimulate hepatic histidase gene expression in rats.

A high protein concentration in the diet induces the gene expression of several amino acid degrading enzymes such as histidase (Hal) in rats. It is important to understand whether the amino acid pattern of the dietary protein affects the gene expression of these enzymes. The purpose of the present work was to study the effect of a histidine-imbalanced diet on the activity and mRNA concentration of rat hepatic histidase. Seven groups of six rats were fed one of the following diets: 1) 6% casein (basal), 2) 20% casein, 3) 35% casein, 4) an imbalance diet containing 6% casein plus a mixture of indispensable amino acids (IAA) equivalent to a 20% casein diet without histidine (I-20), 5) 6% casein plus a mixture of IAA equivalent to a 35% casein diet without histidine (I-35), 6) a corrected diet containing 6% casein plus IAA including histidine equivalent to a 20% casein diet, 7) a corrected diet containing 6% casein plus IAA including histidine equivalent to a 35% casein diet. Serum histidine concentration was inversely proportional to the protein content of the diet, and it was significantly higher in rats fed the corrected diets compared to their respective imbalanced diet groups. Hal activity increased as the protein content of the diet increased. Greater histidine imbalance resulted in lower food intake and higher Hal activity. Rats fed histidine-corrected diets had lower activity than their respective imbalanced groups. Differences in Hal activity were associated with differences in the concentration of Hal mRNA. These results indicate that rats fed a histidine-imbalanced diet exhibit reduced food intake and weight gain and increased Hal gene expression as a consequence of an increased amino acid catabolism.     

Effects of dietary proteins on lipogenic enzymes in rat liver

When fasted rats were fed fat-free diets containing various sources of protein for 3 d, the activities of liver glucose-6-phosphate dehydrogenase, malic enzyme, acetyl-CoA carboxylase and fatty acid synthetase were markedly lower in rats fed soybean protein or gluten than in those fed casein or fish protein. Since malic enzyme mRNA activity was not low in the soybean protein-fed animals, the translation of malic enzyme appears to be suppressed by dietary soybean protein. The incorporation of tritiated water into liver fatty acids was significantly lower in animals fed soybean protein than in those fed casein. The triglyceride levels in plasma and especially in liver were also lower in the groups fed soybean and gluten than in the groups fed casein and fish. In addition, when dietary soybean protein was replaced with amino acids to simulate casein or soybean protein, the effects on the levels of lipogenic enzymes were still found but were not as great. Thus, some effects can be ascribed to the protein itself and some to the amino acid composition of the diet.